The preparation of soft gelatin capsules for a radioactive tracer study

Clinical doses are developed for the oral coadministration of radiolabeled and nonlabeled forms of a poorly soluble investigational compound: OPC-41061. The release rates of the labeled and nonlabeled forms are equated and matched to the release rate of the polymer spray-dried form of the drug in the proposed market product. The study involves the physicochemical characterization of the powders using thermal analysis and dissolution testing, development and extemporaneous manufacture of liquid-filled soft gelatin capsules, and dissolution and stability testing of the final dosage form. Thermal analysis indicated that the labeled powder was amorphous and that the nonlabeled powder, which had been jet-milled, was crystalline. Dissolution testing of the jet-milled and spray-dried powders indicated that the former was released at a significantly slower rate. A liquid formulation containing 25% dimethyl acetamide and 75% polyethylene glycol 400 (PEG 400) solubilized the desired dose of 60 mg and exhibited a drug profile that was similar to the spray-dried formulation. The final formulation was a soft gelatin capsule containing 60 mg of drug, including 100 microCi radioactivity, dissolved in 0.8 ml of a 25% dimethyl acetamide/75% PEG 400 solution. The formulation was chemically and physically stable for a period greater than the duration of the study.